Biomedical subjects

A Resch

Publications and source records attributed to A Resch.

At least 19 recordsLinked to original sources

PubMed2004

Atopic disease and its determinants -- a focus on the potential role of childhood infection.

BACKGROUND: Atopic diseases develop on a genetic background and are modulated by environmental factors among which some infectious diseases are thought to have a protective influence. OBJECTIVE: The aim of this study was to determine the influence of infectious diseases in younger ages, bacterial and viral, on atopic diseases and sensitization to aero- and food-allergens in adults. METHODS: A population-based sample of 4262 subjects aged 25-74 years were interviewed concerning their history of infectious disease within the first 18 years of life. Information about allergic disease, including atopic eczema, allergic rhinitis (AR), and asthma was obtained. A blood sample was drawn and analysed for allergen-specific IgE antibodies against food- and aero-allergens. RESULTS: Multiple logistic regression analyses identified viral infection to be associated with AR (adjusted odds ratio (OR) = 1.39; 95% confidence interval (95% CI): 1.13-1.72) and sensitization to aeroallergens (OR = 1.21; 95% CI: 1.05-1.41). Bacterial disease was a negative predictor for atopy development in the subgroup of patients sensitized to nutritional allergens with concomitant atopic eczema (OR = 0.34; 95% CI: 0.11-0.99), AR (OR = 0.67; 95% CI: 0.42-1.07), or asthma (OR = 0.41; 95% CI: 0.19-0.87). Influences of viral and bacterial infection on AR differed with regard to family history of atopic disease. CONCLUSION: In our study population, history of viral infection was consistently positively associated with AR. Our data suggests that bacterial infections might be preventive for specific subgroups of atopy.

Adult↗

PubMed2001

Genome-wide detection of alternative splicing in expressed sequences of human genes.

We have identified 6201 alternative splice relationships in human genes, through a genome-wide analysis of expressed sequence tags (ESTs). Starting with approximately 2.1 million human mRNA and EST sequences, we mapped expressed sequences onto the draft human genome sequence and only accepted splices that obeyed the standard splice site consensus. A large fraction (47%) of these were observed multiple times, indicating that they comprise a substantial fraction of the mRNA species. The vast majority of the detected alternative forms appear to be novel, and produce highly specific, biologically meaningful control of function in both known and novel human genes, e.g. specific removal of the lysosomal targeting signal from HLA-DM beta chain, replacement of the C-terminal transmembrane domain and cytoplasmic tail in an FC receptor beta chain homolog with a different transmembrane domain and cytoplasmic tail, likely modulating its signal transduction activity. Our data indicate that a large proportion of human genes, probably 42% or more, are alternatively spliced, but that this appears to be observed mainly in certain types of molecules (e.g. cell surface receptors) and systemic functions, particularly the immune system and nervous system. These results provide a comprehensive dataset for understanding the role of alternative splicing in the human genome, accessible at http://www.bioinformatics.ucla.edu/HASDB.

Alternative Splicing↗

PubMed2001

Selenoprotein synthesis in archaea.

The availability of the genome sequences from several archaea has facilitated the identification of the encoded selenoproteins and also of most of the components of the machinery for selenocysteine biosynthesis and insertion. Until now, selenoproteins have been identified solely in species of the genera Methanococcus (M.) and Methanopyrus. Apart from selenophosphate synthetase, they include only enzymes with a function in energy metabolism. Like in bacteria and eukarya, selenocysteine insertion is directed by a UGA codon in the mRNA and involves the action of a specific tRNA and of selenophosphate as the selenium donor. Major differences to the bacterial system, however, are that no homolog for the bacterial selenocysteine synthase was found and, especially, that the SECIS element of the mRNA is positioned in the 3' nontranslated region. The characterisation of a homolog for the bacterial SelB protein showed that it does not bind to the SECIS element necessitating the activity of at least a second protein. The use of the genetic system of M. maripaludis allowed the heterologous expression of a selenoprotein gene from M. jannaschii and will facilitate the elucidation of the mechanism of the selenocysteine insertion process in the future.

Amino Acid Sequence↗

PubMed2001

[Mediastinal Hodgkin lymphomas in computerized tomography. Comparison of exact CT-assisted volumetry and volume assessment using simple geometric models].

BACKGROUND: The importance of the size of the primary tumor in lymphomas and its size after treatment is still uncertain. Assuming a prognostic relevance, an assessment of tumor volume before and after induction of chemotherapy has been performed in the pediatric Hodgkin's disease study (HD-90). Since an exact CT-scan-based volumetric tumor assessment is time-consuming and in some centers not possible, the tumor volume is often estimated based on simple geometric approximations. Aim of this study was the development of an easy to apply and nearly exact model of volume estimation compared to CT-scan-based tumor volume measurements. MATERIAL AND METHODS: Thirty computed tomographies (CT) of mediastinal Hodgkin lymphomas of children aged 5 to 16 years have been examined. The CT scans were digitalized using a CCD camera combined with a frame grabber. Applying the Global Lab image software, the true tumor volume was determined excluding local organs, which did not belong to the lymphoma. Subsequently, volumes were assessed using simple geometric models (block, ellipsoid, octaeder) by using the maximum diameters of the tumor. The differences between the volume of the geometric models and the true volume, based on the CT scan evaluation, were compared. RESULTS: The maximum diameters of a tumor can be used to calculate its volume based on simple geometric models. The model "block" overestimates the volume by 89 to 268%. The model "ellipsoid" overestimates the volume on average by 29%. The model "octaeder" underestimates the volume on average by 18%. A division of the block volume by 2.3 approximated the geometric closest to the true volume: the average volume was overestimated by 2% in tumors with a volume larger than 20 ml. No model was sufficient to approximate tumors with a volume of less than 20 ml. CONCLUSIONS: For the estimation of tumor volumes in mediastinal Hodgkin lymphomas exceeding 20 ml, the formula "block/2.3" results in the closest approximation compared to the true volume. In the course of clinical studies it might be helpful to apply this formula to determine the prognostic relevance of the tumor size and its development under therapy.

Adolescent↗

PubMed2001

Heterologous expression of archaeal selenoprotein genes directed by the SECIS element located in the 3' non-translated region.

Previous in silico analysis of selenoprotein genes in Archaea revealed that the selenocysteine insertion (SECIS) motif necessary to recode UGA with selenocysteine was not adjacent to the UGA codon as is found in Bacteria. Rather, paralogous stem-loop structures are located in the 3' untranslated region (3' UTR), reminiscent of the situation in Eukarya. To assess the function of such putative SECIS elements, the Methanococcus jannaschii MJ0029 (fruA, which encodes the A subunit of the coenzyme F420-reducing hydrogenase) mRNA was mapped in vivo and probed enzymatically in vitro. It was shown that the SECIS element is indeed transcribed as part of the respective mRNA and that its secondary structure corresponds to that predicted by RNA folding programs. Its ability to direct selenocysteine insertion in vivo was demonstrated by the heterologous expression of MJ0029 in Methanococcus maripaludis, resulting in the synthesis of an additional selenoprotein, as analysed by 75Se labelling. The selective advantage of moving the SECIS element in the untranslated region may confer the ability to insert more than one selenocysteine into a single polypeptide. Evidence for this assumption was provided by the finding that the M. maripaludis genome contains an open reading frame with two in frame TGA codons, followed by a stem-loop structure in the 3' UTR of the mRNA that corresponds to the archaeal SECIS element.

3' Untranslated Regions↗

PubMed2001

Escherichia coli O157 infections and unpasteurised milk.

We report on two children with Escherichia coli O157 infection, one of whom developed haemolytic uraemic syndrome (HUS). Both had drunk raw cows or goats milk in the week before their illness. Molecular subtyping identified a sorbitol fermenting Escherichia coli O157:H isolate from a dairy cow. This isolate differed from Shiga toxin producing O157:H strains isolated from the 6 year old boy with HUS. This result underlines the need to search for other causes of infection, despite documented consumption of unpasteurised milk. In the second patient, human sorbitol non-fermenting O157:H isolates and animal isolates from goats were indistinguishable. The isolation of indistinguishable sorbitol non-fermenting Escherichia coli O157:H from contact animals supports the association between HUS and consumption of raw goats milk, and re-emphasises the importance of pasteurising milk.

Animals↗

PubMed2000

Effect of distortions and asymmetry in MR images on radiotherapeutic treatment planning.

Before using MR-images for radiotherapeutic treatment planning, it is necessary to check whether geometrical distortions influence the calculated dose distribution. In this study, 27 MRI units from different manufacturers and with different magnetic field strengths were investigated. First, all geometrical distortions and asymmetry were determined by specially defined parameters. Virtual planning target volume and organ of risk were drawn into MR images from different units and optimized dose distributions were calculated. The resulting field parameters were then transferred to the reference geometry. Geometric distortions caused small variations of the dose maximum (+/-0.5%). Twenty-five percent of the investigated calculated dose distributions showed an increase of the 95% isodose volume, 60% a decrease. The dose deviations in the organ of risk were comparable with the dose deviations in the planning target volume (PTV). This study has shown that measurements of geometrical distortions and asymmetry are necessary for MR-assisted treatment planning. For evaluation, we recommend dose calculations with hypothetical PTV's and organs of risk. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 46-50 (2000).

Electromagnetic Fields↗

PubMed2000

Ultrasound and X-ray-based bone densitometry in patients with anorexia nervosa.

In 20 patients (mean age 23+/-5 years) with anorexia nervosa (AN), bone mass was evaluated by broadband ultrasound attenuation (BUA) of the calcaneus, peripheral quantitative computed tomography (pQCT) of the distal radius, and dual X-ray absorptiometry (DXA) of the lumbar spine and the hip. Compared with 20 age- and sex- matched healthy controls, patients with AN showed marked osteopenia at all measuring sites. Values of BUA (33.0+/-9 dB/MHz vs. 51.0+/-5.7 dB/MHz; P<0.0001) and of BMD of all regions of the hip (e.g., femoral neck: 0.71+/-0.13 g/cm(2) versus 0.89+/-0.07 g/cm(2); P<0.001), lumbar spine (0.82+/-0.15 g/cm(2) versus 1.24+/-0.06 g/cm(2); P<0.003) and total BMD of the peripheral radius (303.2+/-75 g/cm(3) versus 369.4+/-53.2 g/cm(3), P<0.001) were significantly reduced. Calculating a Z-score we found the most prominent differences between AN and controls by BUA of the calcaneus (-3.2+/-1.6), followed by DXA at the lumbar spine (-2.9+/-2.2) and the hip (femoral neck -2.1+/-1.7) and by pQCT at the distal radius (total BMD -1.2+/-2.0). There were highly significant correlations between BUA of the calcaneus and BMD of the femoral neck (r = 0.78, P<0.0001) and lumbar spine (r = 0.75, P<0.0001) as well as between BMD values of the femoral neck and lumbar spine (r = 0.95; P<0.0001). In addition, there were significant correlations (P<0.001) between body mass index (BMI) and the three different measuring sites and between the duration of the disease and BUA (r = 0.5, P<0.05). Our data suggest that BUA of the calcaneus is a valuable tool in the management of osteoporosis. Being a fast, radiation-free investigation method of good acceptance, it may be well suited for an assessment of the skeletal status in patients with AN.

Absorptiometry, Photon↗

PubMed1999

[Contour defects after breast preserving therapy of breast carcinoma. Primary and secondary possibilities of correction].

BACKGROUND: Breast conserving treatment is increasing for primary treatment of breast carcinoma because of the importance of the cosmetic outcome. PATIENTS AND METHOD: We examined 195 patients after breast conserving therapy which was performed between 1983 and 1992. For evaluation of the cosmetic result symmetry, contour of the breast and location of the areola were examined. Radiation effect on breast tissue was evaluated by the Lent score. 72% of the patients had been treated with quadrantectomy and 28% with lumpectomy. RESULTS: Deformities of the contour were visible in 59% of the patients depending on the primary location of the tumor. Lumpectomy from medial quadrants caused poor results. Dislocation of the areola of more than 2 cm was detected in 32% of the patients. The dislocation depended on the primary kind of incision and resulted in 89% of the patients after a radial incision and only in 11% after curvilinear incisions. Telangiectasias were absent in 84% of the patients, the others showed telangiectasias Grade 1 to 3. In 48% of the patients no signs of fibrosis could be detected, in 49% fibrosis Grade 1 to 2 was found. 68% of the patients estimated the cosmetic result as very good or good. Only 10% of the patients estimated the result as fair or bad. The examiner estimated the results as good or very good in 28%. Examples of operative procedures for primary and secondary correction are demonstrated. CONCLUSIONS: Our results showed an adverse effect of long radial incisions. For lumpectomy and axillary node dissection separate incisions should be used. Correction of contour deformities should be done primarily in breast conserving procedures. This is possible by using modified reduction mammaplasties, local flaps of the breast tissue or switching a latissimus dorsi muscle flap. For secondary correction of defects after breast conserving treatment a latissimus dorsi muscle can be used as well as z-plasty for scar contracture.

Brachytherapy↗

PubMed1999

Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs.

In this study, we have examined the influence of initiation factors on translation initiation of leaderless mRNAs whose 5'-terminal residues are the A of the AUG initiating codon. A 1:1 ratio of initiation factors to ribosomes abolished ternary complex formation at the authentic start codon of different leaderless mRNAs. Supporting this observation, in vitro translation assays using limiting ribosome concentrations with competing leaderless lambda cl and Escherichia coli ompA mRNAs, the latter containing a canonical ribosome binding site, revealed reduced cl synthesis relative to OmpA in the presence of added initiation factors. Using in vitro toeprinting and in vitro translation assays, we show that this effect can be attributed to IF3. Moreover, in vivo studies revealed that the translational efficiency of a leaderless reporter gene is decreased with increased IF3 levels. These studies are corroborated by the observed increased translational efficiency of a leaderless reporter construct in an infC mutant strain unable to discriminate against non-standard start codons. These results suggest that, in the absence of a leader or a Shine-Dalgarno sequence, the function(s) of IF3 limits stable 30S ternary complex formation.

5' Untranslated Regions↗

PubMed1999

Antithrombogenic coating of stents using a biodegradable drug delivery technology.

To reduce the thrombogenic properties of coronary artery stents, a biodegradable polylactic acid (PLA) stent coating with an incorporated thrombin inhibitor and a platelet aggregation inhibitor has been developed. In an ex vivo human stasis model, its effect on platelets, plasmatic coagulation and its release characteristics were studied using whole blood. Bare steel and bare gold-surface stents were compared to steel and gold-surface stents coated with PLA (30 kDa) containing 5% polyethyleneglycol (PEG)-hirudin and 1% iloprost, with an empty tube as control. Markers of activated coagulation (prothrombin fragment F1-2 and thrombin-antithrombin III complex, TAT), were assayed and the release of drugs from the coating was assessed by aPTT and collagen-induced platelet aggregation. Bare steel and gold stents were completely covered by a blood clot, and high levels of coagulation markers (F1-2 fragment and TAT) were detected. No differences in the thrombogenic properties were found between bare gold or steel stents. Coated stents were free of blood clots and only minor elevations of markers were detected. Release data from in-vitro studies over 90 days showed a gradual release of the drugs with an initial exponential release characteristic for PEG-hirudin, slow release of iloprost and a 10% degradation of the PLA carrier. This drug releasing biodegradable coating effectively reduced thrombus formation independent of the metallic surface.

Antithrombins↗

PubMed1998

Discrimination of 5'-terminal start codons by translation initiation factor 3 is mediated by ribosomal protein S1.

The interrelation between ribosomal protein S1 and IF3 in recognition/discrimination of 5'-terminal start codons by 30S ribosomes has been studied using in vitro toeprinting. The study has been performed with two naturally occurring leaderless mRNAs, lambda cI and phage r1t rro mRNA, as well as with an artificial leaderless mRNA derived from the E. coli ompA gene. We show that in the absence of S1, IF3 does not discriminate against the authentic 5'-terminal start codon of both cI and rro mRNA. Since IF3 was able to exert its proofreading function for initiator tRNA(fMet) on 30S ribosomes lacking S1, this observation cannot be attributed to a lack of binding to or action of IF3 on 30S(-S1) ribosomes. In contrast to leaderless mRNAs, ternary complex formation occurs in the presence of IF3 with 30S ribosomes when the start codon is preceded by a short 20-nucleotide 5'-untranslated region containing a canonical Shine and Dalgarno sequence. This suggests that 5'-terminal start codons are recognised by IF3 as non-standard because of the lack of 16S rRNA-mRNA contacts.

Bacteriophage lambda↗

PubMed1998

Evidence that tamoxifen preserves bone density in late postmenopausal women with breast cancer.

Tamoxifen, which is used for treating breast cancer, exhibits estrogenic and antiestrogenic characteristics, depending on the tissue. In the human breast it acts as an antiestrogen, whereas estrogenic effects have been reported on endometrium and bone. The purpose of this study was to determine whether tamoxifen (TAM) prevents bone loss in elderly, postmenopausal women. Bone mineral density of the lumbar spine (SBD) was measured in elderly women (at least 10 years after menopause) 5 years after stage I or II breast cancer (n = 111). The results showed that SBD in untreated patients (n = 74) was significantly lower (p < 0.05) than SBD in patients (n = 37) treated with TAM over 5 years. In a subgroup of patients (n = 24) with positive estrogen receptor status, changes in SBD 12 months after discontinuation of 5-year TAM therapy were measured and compared with the changes of extended TAM treatment over a sixth year. Twelve months after withdrawal of 5-year TAM medication (n = 11) bone density decreased significantly (- 4.8+/-2.5%; p > 0.05), whereas in the group of women (n = 13) receiving extended TAM medication (20 mg) for an additional 12 months, SBD ( + 1.9+/-3.5 %) was maintained during the observation period, and was significantly higher when compared with the group of untreated patients (p <0.05). We conclude that tamoxifen has a preventive effect on trabecular bone loss at the lumbar spine, when compared to age-matched data and to untreated women with breast cancer in the late menopause. Our data give evidence of benefits to bone density provided by prolonged administration in patients after breast cancer and at risk of osteoporosis.

Aged↗

PubMed1997

Impact of spinal degenerative changes on the evaluation of bone mineral density with dual energy X-ray absorptiometry (DXA).

The purpose of this study is to evaluate degenerative factors in a postmenopausal patient group and differentiate the influence on bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA). The patients and methods included an investigation of 144 postmenopausal women (mean 63.3 years) with PA-DXA of the spine. Degenerative factors (osteophytes, osteochondrosis, scoliosis, and vascular calcification) were evaluated from plain lumbar radiographs, their estimated probability was analyzed as a function of age, and their influence on BMD measured by PA-DXA was determined. The results of the study revealed osteophytes in 45.8%, vascular calcifications in 24.3%, scoliosis in 22.2%, osteochondrosis in 21.5%. The estimated probability for degenerative factors increased from 35 to 80% in the 55- to 70- year age group. Osteophytes and osteochondrosis were associated with up to a 14% increase in BMD values (P < 0.001). Vascular calcifications showed a positive trend, whereas scoliosis did not show a discernible influence.We concluded that degenerative factors, except for scoliosis, showed an influence on BMD as measured by DXA. Their prevalence increased rapidly between 55 and 70 years of age. Interpretation of PA-DXA spine data for subjects of or above this age range should be complemented by plain film radiographs.

Absorptiometry, Photon↗

PubMed1997

Requirements for ribosomal protein S1 for translation initiation of mRNAs with and without a 5' leader sequence.

It has previously been proposed that Escherichia coli ribosomal protein S1 is required for the translation of highly structured mRNAs. In this study, we have examined the influence of structural features at or near the start codon of different mRNAs. The requirement for ribosomal protein S1 for translation initiation was determined when (i) the ribosome-binding site (RBS) was either preceded by a 5' non-translated leader sequence; (ii) the RBS was located 5' proximal to a mRNA start codon; and (iii) the start codon was the 5' terminal codon as exemplified by leaderless mRNAs. In vitro translation studies revealed that the leaderless lambda cl mRNA is translated with Bacillus stearothermophilusribosomes, naturally lacking a ribosomal protein S1 homologue, whereas ompA mRNA containing a 5' leader is not. These studies have been verified by toeprinting with E. coli ribosomes depleted for S1. We have shown that S1 is required for ternary complex formation on ompA mRNA but not for leaderless mRNAs or for mRNAs in which the RBS is close to the 5' end.

5' Untranslated Regions↗

PubMed1997

Association of midoesophageal diverticula with oesophageal motor disorders. Videofluoroscopy and manometry.

PURPOSE: To evaluate the prevalence and clinical significance of associated oesophageal motor disorders in patients with midoesophageal diverticula. MATERIAL AND METHODS: We retrospectively reviewed videofluoroscopic and, if available, manometric studies of 30 patients with midoesophageal diverticula. The type of diverticulum and the presence and nature of oesophageal motor disorders were assessed. RESULTS: Videofluoroscopy showed that 24 patients had 26 pulsion-type diverticula and 6 patients had 7 traction-type diverticula. Oesophageal motor disorders were demonstrated in 21 of the 24 patients with pulsion-type diverticula and in 3 of the 6 with traction-type diverticula. Nineteen patients had nonspecific motor disorders, 5 had achalasia, and 5 had gastrooesophageal reflux or oesophagitis. CONCLUSION: Midoesophageal diverticula are most often of the pulsion-type and tend to be associated with an oesophageal motor disorder. Motor disorders are predominantly nonspecific, but achalasia may be encountered as well.

Adult↗

PubMed1996

Downstream box-anti-downstream box interactions are dispensable for translation initiation of leaderless mRNAs.

The downstream box (db) with complementarity to a segment in the penultimate stem of 16S rRNA has been suggested to serve as a recognition element for the ribosome. For some mRNAs, the db has been proposed to act synergistically with the Shine and Dalgarno sequence (SD), while for the leaderless lambda(cI) mRNA it has been suggested to substitute for the SD in translation initiation. To test whether the db-anti-db interaction is required for translation initiation, we have used three different leaderless transcripts, the lambda(cI), phage P2 gene V and Tn1721 tetR mRNA. Using primer extension inhibition analysis (toeprinting), we show that the db does not influence translation initiation complex formation in vitro. In an attempt to demonstrate the simultaneous interactions between the db and anti-db and between the anticodon of initiator tRNA and the start codon, respectively, chemical probing has been employed on cI translation initiation complexes. These studies did not reveal a protection of the bases comprising the putative db in cI. In addition, kinetic toeprinting experiments and in vivo expression studies with cI mRNA showed that the db is dispensable for the initial interaction between ribosome and cI mRNA in the pathway towards formation of the initiation complex.

Kinetics↗

PubMed1995

Dual translational start motif evolutionarily conserved in the holin gene of Bacillus subtilis phage phi 29.

Holins represent phage encoded lysis functions required for transit of the phage murein hydrolases to the periplasm. The Lambda S, phage 21 S, and P22 13 holin genes contain a dual translational start motif, beginning with Met1-Lys2-X-Met3. In all cases both start codons at the 5' end of the respective holin gene are utilized. The resulting polypeptides have opposing functions, with the longer product acting as an inhibitor of the shorter one. The 131-codon gene 14 of Bacillus subtilis phage phi 29 encodes the holin function, whereas the downstream gene 15 codes for a lysozyme. phi 29 Gene 14 begins with Met1-Lys2-Met3. Here, we present in vitro and in vivo evidence for the expression of two protein 14 species consisting of 129 and 131 amino acids, respectively. These data suggest that the lysis control mechanism based on two holin species, which has been shown to be operational in the temperature Escherichia coli phages Lambda and 21, and in the Salmonella typhimurium phage P22, is evolutionarily conserved in the lytic B. subtilis phage phi 29.

Amino Acid Sequence↗